The convenience of administering a single dose of medication which releases active ingredient over an extended period of time as opposed to the administration of a number of single doses at regular intervals has long been recognized in the pharmaceutical art. The advantage to the patient and clinician in having consistent and uniform blood levels of medication over an extended period of time are likewise recognized. In most sustained release preparations known to the pharmaceutical art, medicinal agents are either coated with varying thicknesses of some type of relatively insoluble material or are imbedded into a rigid lattice of resinous material. In such preparations, the object is to continuously provide drug for absorption into the blood stream to replace the amount eliminated while the dosage form is passing through the gastrointestinal tract of the patient.
The conventional approaches to sustained release formulation briefly outlined above can be disadvantageous in that certain classes of active ingredients are not suited to absorption during passage through the gastrointestinal tract due to their physiochemical properties and/or favorable sites of absorption. For example, most acidic medicaments are principally absorbed from the stomach whereas most basic medicaments are absorbed primarily from the intestines. Most medicaments will undergo varying degrees of change in solubility by passage from the acutely acidic conditions of the stomach to the neutral to alkaline conditions of the intestines. For example, ferrous salts are more soluble in the stomach than in the intestines. Finally, there are medicaments, e.g. antacids, which are intended to act in the stomach and therefore lose most beneficial properties when they pass into the intestines.
It is readily apparent in view of the above considerations that a large number of medicaments are not amenable to conventional sustained release formulations which are not retained in the stomach and which release medicament in the intestines. It is equally apparent that a sustained release formulation which is retained in the stomach and which slowly releases medicament over an extended period of time would be eminently suited to such medicaments. Such a sustained release formulation is provided by the present invention.
The principle of sustained release which characterizes the formulations contained in the capsules of the subject invention is unique in the art, i.e. the formulation remains buoyant and freely floating in the gastric fluid for an extended period of time during which substantially all of the medicament contained therein is released into the gastric fluid for absorption. Although many mechanisms of sustained release are recognized in the art and the concept of a floating tablet is known, there is no teaching in the art of a formulation which remains intact and buoyant in the gastric fluid while substantially all of the medicament is released therefrom.